A Trial Within Cohort Feasibility Study Design Comparing Standard of Care Versus Weight Loss (Achieved Through Tirzepatide) for Obesity-related Hypertension in Young Adults

NCT07364175 | Recruiting

• 1 other identifier: R+D: A097457, REC: 25/WA/0268
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Hypertension is the leading risk factor for death globally, affecting approximately 30% of adults in the United Kingdom. Obesity is also a serious and ongoing epidemic, with global obesity rates having more than tripled in men and doubled in women, since 1975. In the United Kingdom, 64% of the adult population are overweight or obese. Hypertension and obesity share a well-established association, with obesity being responsible for the development of hypertension in 40-78% of cases. In young adults, this link between body size and blood pressure (BP) is much stronger that in older adults. Since overweight and obesity are among the most common and modifiable causes of high BP, weight loss induced by lifestyle-changes is recommended for overweight or obese patients with hypertension. However, lifestyle interventions, even when successful, result in only moderate weight loss, which is not maintained in the majority of cases. A meta-analysis of randomised controlled trials demonstrated that lifestyle-interventions lead to an average net weight reduction of 5.1 kg, accompanied by a significant, but modest, \~4 mmHg reduction in BP. Weight loss interventions could play a crucial role in the treatment of obesity-related hypertension in young adults. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, originally developed for the treatment of type 2 diabetes, are safe and clinically effective anti-obesity drugs. Recent data show a 10-20% placebo-adjusted reduction in body weight in overweight or obese adults without diabetes using the GLP-1 analogue semaglutide or the dual GLP-1/GIP receptor agonist tirzepatide, with the majority of weight loss achieved within the initial six months. The substantial weight loss induced by these drugs is accompanied by a significant reduction in BP. Two recent meta-analyses showed that semaglutide is associated with a \~5 mmHg placebo-adjusted reduction in clinic systolic BP (SBP). A sub-study of the SURMOUNT-1 trial reported a \~10 mmHg reduction in 24-h ambulatory SBP with tirzepatide. Most participants in these studies were normotensive or had well-controlled hypertension. Furthermore, antihypertensive medication use declined amongst those receiving anti-obesity drugs meaning the BP-lowering effect of weight loss, elicited by these drugs, is probably underestimated. These data suggest that the new anti-obesity drugs could be effective in managing overweight or obesity-related hypertension. Furthermore, it may be possible to cure hypertension in at least some young adults, removing the need for life-long antihypertensive treatment. However, the magnitude and time course of BP reduction elicited by these new anti-obesity drugs remain uncertain. The primary aim of this feasibility study is to assess the extent and trajectory of BP reduction achieved through intensive weight loss in overweight or obese adults with stage 1 hypertension and compare this to current standard of care measures which uses anti-hypertensive medications and lifestyle advice. The study will utilise a modified trial within cohort approach, using patients based within the clinical pharmacology/hypertension service at Addenbrooke's Hospital, Cambridge.

Conditions

Hypertension; Obesity & Overweight

Keywords

hypertension; obesity; overweight; tirzepatide; GLP-1

Outcome Measures

Primary Outcomes (1)

• Ambulatory systolic blood pressure

  Change in daytime ambulatory systolic blood pressure in the weight loss arm

  Baseline to week 24

Secondary Outcomes (55)

• Ambulatory diastolic blood pressure

  Baseline to week 24

• Clinic systolic blood pressure

  Baseline to week 24

• Clinic diastolic blood pressure

  Baseline to week 24

• Clinic mean arterial pressure

  Baseline to week 24

• Unattended systolic blood pressure

  Baseline to week 24

Study Arms (2)

Tirzepatide [weight loss arm]

EXPERIMENTAL

6 months of treatment with a combined GLP-1/GIP receptor agonist, tirzepatide

Drug: Tirzepatide

Lifestyle advice and anti-hypertensive medications [standard of Care arm]

ACTIVE COMPARATOR

Drug: Anti-Hypertensive medications

Interventions

Tirzepatide DRUG

2.5mg for 4 weeks, 5mg for 4 weeks, 7.5mg for 4 weeks, 10mg for 12 weeks

Tirzepatide [weight loss arm]

Anti-Hypertensive medications DRUG

Anti-hypertensive drug therapy as per local and national guidelines

Lifestyle advice and anti-hypertensive medications [standard of Care arm]

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18 to 40 years (inclusive)
• Body mass index (BMI) ≥27 kg/m2
• Clinical diagnosis of primary (essential) hypertension as per NICE guidance
• Unattended brachial SBP ≥135 and/or DBP ≥85 mmHg and \<160/100 mmHg
• Maximum of one antihypertensive medication

You may not qualify if:

• Anything in medical notes suggesting unsuitable in the opinion of the investigator
• Eligibility criteria for participation in weight loss arm
• Written informed consent
• Aged 18 to 40 years (inclusive)
• Body mass index ≥27 kg/m2
• Clinical diagnosis of primary (essential) hypertension as per NICE guidance
• Unattended brachial SBP ≥135 and/or DBP ≥85 mmHg and \<160/100 mmHg
• Maximum of one antihypertensive medication
• Known or suspected secondary hypertension
• Hypersensitivity to any of the study drugs or excipients
• Currently taking drugs likely to have interactions with tirzepatide
• Diagnosis of type 1 or type 2 diabetes mellitus or current usage of insulin or other injectable drugs for the treatment of diabetes such as but not limited to GLP-1 and GIP receptor agonists
• Prior or planned surgical, endoscopic and/or device-based therapy treatment for obesity
• Self-reported, intentional or unintentional, change in body weight (over \~10%) within \~three months of screening
• Known heart failure or clinically significant valvular heart disease

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Hypertension; Obesity; Overweight

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Physician and Clinical Pharmacologist

Model Details: The study will utilise a modified trial within cohort (TwiC) design for patients under the hypertension/clinical pharmacology clinic. Those who meet the eligibility criteria for randomisation will be randomised to being approached for either: (i) 6 months of treatment with a combined GLP-1/GIP receptor agonist, Tirzepatide \[Group A - Weight loss arm\] (ii) Standard anti-hypertensive treatment and attendance at a 6-month combined research/clinical follow-up visit \[Group B - Standard of Care (SoC) arm\].

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 23, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Access Criteria: Following publication, the data that support the findings of this study will be available from the Chief Investigator/corresponding author upon reasonable request

Locations

GB (1)